Our objective is to determine those changes which allow for transformation of normal cells into neoplastic cells. To this end we have been investigating biochemical properties and regulation of metabolic activities in two minimally deviated tissues. By studying the precancerous, hyperplastic alveolar nodules of mouse mammary glands and the minimal deviation hepatomas of rats, we hope to find early changes which precede or accompany the carcinogenic process. A summary of some of our new approaches are listed below: 1. The rate of DNA synthesis in the cancerous and precancerous mammary tissues is under pituitary regulation. We are now determining which pituitary hormones are responsible and investigating the significance of hormonal dependence of DNA synthesis in the carcinogenic process. 2. The hormonal regulation of xanthine oxidase activity and of synthesis of milk components, particularly fatty acids, as a means of altering the growth rate of the abnormal mammary tissues is also being investigated. 3. The activities of the various cellular compartments must be coordinated so that the cell can function as an integral unit. We are investigating how this coordination is integrated and what changes are initiated in this coordination during the normal and carcinogenic transformations in cellular function which occur with mammary tissues. 4. Cell cultures from normal and neoplastic mammary tissues are being used to investigate factors initiating functional transformations in cellular activity.